PEP-1–PIN1 Promotes Hippocampal Neuronal Cell Survival by Inhibiting Cellular ROS and MAPK Phosphorylation
Jung Hwan Park,
Min Jea Shin,
Gi Soo Youn,
Hyeon Ji Yeo,
Eun Ji Yeo,
Hyun Jung Kwon,
Lee Re Lee,
Na Yeon Kim,
Su Yeon Kwon,
Su Min Kim,
Yong-Jun Cho,
Sung Ho Lee,
Hyo Young Jung,
Dae Won Kim,
Won Sik Eum,
Soo Young Choi
Affiliations
Jung Hwan Park
Department of Biomedical Science and Research Institute of Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea
Min Jea Shin
Department of Biomedical Science and Research Institute of Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea
Gi Soo Youn
Department of Biomedical Science and Research Institute of Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea
Hyeon Ji Yeo
Department of Biomedical Science and Research Institute of Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea
Eun Ji Yeo
Department of Biomedical Science and Research Institute of Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea
Hyun Jung Kwon
Department of Biomedical Science and Research Institute of Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea
Lee Re Lee
Department of Biomedical Science and Research Institute of Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea
Na Yeon Kim
Department of Biomedical Science and Research Institute of Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea
Su Yeon Kwon
Department of Biomedical Science and Research Institute of Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea
Su Min Kim
Department of Biomedical Science and Research Institute of Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea
Yong-Jun Cho
Department of Neurosurgery, Hallym University Medical Center, Chuncheon 24253, Republic of Korea
Sung Ho Lee
Department of Biomedical Science and Research Institute of Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea
Hyo Young Jung
Department of Veterinary Medicine & Institute of Veterinary Science, Chungnam National University, Daejeon 34134, Republic of Korea
Dae Won Kim
Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung 25457, Republic of Korea
Won Sik Eum
Department of Biomedical Science and Research Institute of Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea
Soo Young Choi
Department of Biomedical Science and Research Institute of Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea
Background: The peptidyl-prolyl isomerase (PIN1) plays a vital role in cellular processes, including intracellular signaling and apoptosis. While oxidative stress is considered one of the primary mechanisms of pathogenesis in brain ischemic injury, the precise function of PIN1 in this disease remains to be elucidated. Objective: We constructed a cell-permeable PEP-1–PIN1 fusion protein and investigated PIN1’s function in HT-22 hippocampal cells as well as in a brain ischemic injury gerbil model. Methods: Transduction of PEP-1–PIN1 into HT-22 cells and signaling pathways were determined by Western blot analysis. Intracellular reactive oxygen species (ROS) production and DNA damage was confirmed by DCF-DA and TUNEL staining. Cell viability was determined by MTT assay. Protective effects of PEP-1-PIN1 against ischemic injury were examined using immunohistochemistry. Results: PEP-1–PIN1, when transduced into HT-22 hippocampal cells, inhibited cell death in H2O2-treated cells and markedly reduced DNA fragmentation and ROS production. This fusion protein also reduced phosphorylation of mitogen-activated protein kinase (MAPK) and modulated expression levels of apoptosis-signaling proteins in HT-22 cells. Furthermore, PEP-1–PIN1 was distributed in gerbil hippocampus neuronal cells after passing through the blood–brain barrier (BBB) and significantly protected against neuronal cell death and also decreased activation of microglia and astrocytes in an ischemic injury gerbil model. Conclusions: These results indicate that PEP-1–PIN1 can inhibit ischemic brain injury by reducing cellular ROS levels and regulating MAPK and apoptosis-signaling pathways, suggesting that PIN1 plays a protective role in H2O2-treated HT-22 cells and ischemic injury gerbil model.